stereochemistry - chirality · 2020. 10. 28. · 4 •every object has a mirror image: mirror...

Stereochemistry - Chirality

Chapter 5

Organic Chemistry, 8th Edition

John E. McMurry

2

Isomerism

• The two major classes of isomers are constitutional isomers

and stereoisomers.

Constitutional/structural isomers have different IUPAC

names, different physical and chemical properties, and

may have different functional groups.

Stereoisomers differ only in the way the atoms are

oriented in space. They have identical IUPAC names

(except for a prefix like cis or trans). They always have the

same functional group(s).

• A particular three-dimensional arrangement is called a

configuration. Stereoisomers differ in configuration.

3

Stereoisomers

4

• Every object has a mirror image: mirror images may or may

not be superimposable.

• Some molecules are like hands. Left and right hands are

mirror images, but they are not identical, or superimposable.

Chirality

5

• A and B are stereoisomers—specifically, they are

enantiomers.

• A carbon atom with four different groups is a tetrahedral

stereogenic center.

Chirality

Tartaric acid

A B

enantiomeri

Louis Pasteur

7

Chirality

8

Chirality and Symmetry

9

Amines are Achiral

10

Stereogenic Centers

11

• To locate a stereogenic center, examine each tetrahedral

carbon atom in a molecule, and look at the four groups—not

the four atoms—bonded to it.

• Always omit from consideration all C atoms that cannot be

tetrahedral stereogenic centers. These include

CH2 and CH3 groups

Any sp or sp2 hybridized C

Stereogenic Centers

12

• Larger organic molecules can have two, three or even

hundreds of stereogenic centers.

Stereogenic Centers

13

Stereogenic Centers

Palytoxin: 64 chiral centers

14

• Stereogenic centers may also occur at carbon atoms that are part of a

ring.

• To find stereogenic centers on ring carbons, always draw the rings as flat

polygons, and look for tetrahedral carbons that are bonded to four different

groups.

Cyclic Compounds

15

Cyclic Compounds

Binaphtalenes

Biphenyl

Stereoisomeris from Hindered Rotation

Enantiomers

Allenes

18

• A sterogenic center is a sufficient but not necessary condition

for chirality.

• With one stereogenic center, a molecule will always be chiral.

• With two or more stereogenic centers, a molecule may or

may not be chiral.

• Achiral molecules usually contain a plane of symmetry but

chiral molecules do not.

• A plane of symmetry is a mirror plane that cuts the molecule

in half, so that one half of the molecule is a reflection of the

other half.

Chirality and Symmetry

19

• Naming enantiomers with the prefixes R or S is called the

Cahn-Ingold-Prelog system.

• Priority rule 1. The atom of highest atomic number gets the

highest priority (1).

Cahn-Ingold-Prelog System

20

• Priority rule 2. If two atoms on a stereogenic center are the same,assign priority based on the atomic number of the atoms bonded to these

atoms. One atom of higher atomic number determines the higher priority.


21

• Priority rule 3. If two isotopes are bonded to the stereogenic center,assign priorities in order of decreasing mass number. Thus, in comparing

the three isotopes of hydrogen, the order of priorities is:


22

• Priority rule 4. To assign a priority to an atom that is part of a multiplebond, treat a multiply bonded atom as an equivalent number of singly

bonded atoms. For example, the C of a C=O is considered to be bonded

to two O atoms.


23


24


25


26

• The physical properties of two enantiomers are identical

except for how they interact with plane-polarized light.

• In ordinary light the electric vector oscillates in all planes

perpendicular to the propagation direction.

• In plane polarized light the vector oscillates in a single plane.

Polarized light is obtained with a polarizer.

Optical Activity

plane-polarized

light

unpolarized

light

electric

vector

magnetic

vector

propagation

27

• In a polarimeter polarized light travels through a sample tube

containing an organic compound.

• With achiral compounds, the light that exits the sample tube

remains unchanged. A compound that does not change the

plane of polarized light is said to be optically inactive.

Optical Activity

28

• Two enantiomers rotate plane-polarized light to an equal extent but in

opposite directions.

•No relationship exists between R and S prefixes and the (+) and (-)

designations that indicate optical rotation.

dextrorotatory

(+)

levorotatory

(–)

Optically

active

Optically

active

Optical Activity

Optically

inactive

+ a - a a = 0

(S)-(+) (S)-(-)

29

• Specific rotation is a standardized physical constant for the amount that a

chiral compound rotates plane-polarized light. Specific rotation [a] is

defined using a specific sample tube length (l, in dm), concentration (c in

g/mL for pure liquids [=d]; g/100mL for solutions), temperature (generally

250C) and wavelength (generally 589 nm).

Optical Activity

(g/ml or g/100ml)

30

• An equal amount of two enantiomers is called a racemic mixture or a

racemate. A racemic mixture is optically inactive. Because two

enantiomers rotate plane-polarized light to an equal extent but in opposite

directions, the rotations cancel, and no rotation is observed.

Racemic Mixtures

Property (+) Enantiomer (-) Enantiomer Racemic mixture

melting point identical may be different

boiling point identical may be different

optical rotation + α - α 0

31

• Enantiomeric excess (optical purity) is a measurement of how

much one enantiomer is present in excess of the racemic

mixture.

ee = % of one enantiomer - % of the other enantiomer.

• The enantiomeric excess can also be calculated if the specific

rotation [a] of a mixture and the specific rotation [a] of a pure

enantiomer are known.

ee = ([a] mixture/[a] pure enantiomer) x 100.

Optical Purity

[S] + [R]

[S] - [R] e.e. = x 100

(e.e.) with respect to relative % of the two enantiomers :

[S] = contration of enantiomer S

[R] = concentration of enantiomer R

[S]

50

60

70

80

90

95

98

99

e.e.

00

20

40

60

80

90

94

98

Enantiomeric excess

33

• Two enantiomers have exactly the same chemical properties except for

their reaction with chiral non-racemic reagents.

• Many drugs are chiral and often must react with a chiral receptor or chiral

enzyme to be effective. One enantiomer of a drug may effectively treat a

disease whereas its mirror image may be ineffective or toxic.

Chemical Properties of Enantiomers

Thalidomide

35

• Research suggests that the odor of a particular molecule is determined

more by its shape than by the presence of a particular functional group.

• Because enantiomers interact with chiral smell receptors, some

enantiomers have different odors.

Chemical Properties of Enantiomers

36

3 point theory:

receptor receptor

Chiral Recognition

37

Diastereomers

enantiomers enantiomers

diastereomers

(2S,3R)-2,3-dibromopentane

• When a compound has more than one stereogenic center, R and S configurations must be

assigned to each of them.

38

Meso Compounds

enantiomers identical

diastereomers

39

Meso Compounds

• Meso compounds contain a plane of symmetry, and are

achiral.

=

40

• Consider 1,3-dibromocyclopentane. Since it has two stereogenic centers, it

has a maximum of four stereoisomers.

• cis isomer (A) and trans isomer (B) are stereoisomers but not mirror

images.

Diastereomers

41

• The cis isomer is superimposable on its mirror image, making the images

identical. Thus, A is an achiral meso compound.

Diastereomers

42

• The trans isomer is not superimposable on its mirror image, labeled C,

making B and C different compounds. B and C are enantiomers.

Diastereomers

43

• Diastereomers have different physical properties, and

therefore can be separated by common physical techniques.

Diastereomers

Isomeria

Conformeri

Stereoisomeri che si formano

per rotazione attorno a un

legame semplice

45

• Enantiomers have identical physical properties and

can not be separated by conventional physical

techniques (distillation, crystallization, etc).

• The separation of enantiomers in a racemic mixture is

called resolution.

Separation of Enantiomers

46

diastereomers

+A

racemic

mixture (R) + (S)

separation

(R)-B is

recovered

B

single

enantiomer(R)

B resolving agent

A―B

(S,R)

+ A―B

(R,R)

A―B(S,R)

A―B(R,R)

A(R)

A(S)

Resolution of Enantiomers

47


48

+

+

1) Separation of

diastereoisomeric

salts

Racemic mixture

(R) + (S)

(R,S)

(S,S)

S S

R SR

S

S

Resolving agent

2) HCl


Brucina (2,3-dimetossistricnina) morfina

stereochemistry - chirality · 2020. 10. 28. · 4 •every object has a mirror image: mirror...

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